Pulmonary Hypertension, COVID-19
Conditions
Keywords
Acute Pulmonary Hypertension
Brief summary
This is an open-label, multicentre study evaluating the effect, safety and tolerability of the two regioisomers 1-(nitrosooxy)propan-2-ol and 2-(nitrosooxy)propan-1-ol (PDNO) infusion given to COVID-19 patients with acute pulmonary hypertension (aPH) and/or acute cor pulmonale (ACP).
Interventions
Placebo (NaCl, commercially available dilution solution for parenteral use, 9 mg/mL)
DRUGPDNO
PDNO consists of propylene glycol (1,2-propanediol, PD) chemically combined with NO (to be donated). The drug substance is formulated as an inherent mixture of 4 structure analogues. The mixture consists of an equilibrium of the 2 regioisomers 1-(nitrosooxy) propan-2-ol and 2-(nitrosooxy) propan-1-ol. In addition, each regioisomer is a racemic mixture.
Sponsors
Vinnova
Attgeno AB
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Observational period with placebo treatment, followed by treatment with PDNO.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand and willing to sign an ICF * Male and female patients at least 18 years of age * Diagnosed with COVID-19 at admission to the ICU * Diagnosed with echocardiographic signs of pulmonary artery systolic pressure (PASP) \> 40 mmHg
Exclusion criteria
* History of chronic pulmonary hypertension (PH), as judged by the Investigator at screening * Known New York Heart Association (NYHA) Functional Class III or IV symptoms * Left heart failure with ejection fraction (EF) \< 35% * Acute coronary syndrome * Body Mass Index (BMI) \> 45 kg/m\^2 * Estimated glomerular filtration rate (eGFR) \< 30 mL/min * MetHb \> 3% * PCO2 \> 7 * Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) at screening * Haemoglobin \< 80 g/dL * Thrombocytopenia (platelet count \< 80000/mm\^3) * Prothrombin time International ratio (INR) \> 1.4 * Pregnancy, or a positive pregnancy test * Ongoing daily treatment the last 3 days with non-steroidal anti-inflammatory drugs * Known active malignancy within the past 3 years * History of allergy/hypersensitivity to PD or ongoing allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to PDNO * History of any other clinically significant disease or disorder * Participation in any interventional clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state. | During 24 hours | Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR), as measured with a pulmonary artery catheter (PAC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent AEs, SAEs, and AESI. | Through study completion (i.e., Day 30) | * Treatment-emergent adverse events (AEs) * Treatment-emergent serious AEs (SAEs) * Treatment-emergent AEs of special interest (AESI) |
| Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent changes in vital signs, ECG abnormalities, and laboratory abnormalities. | From baseline until Day 7 | * Treatment-emergent changes in vital signs (blood pressure, pulse, oxygen saturation, respiratory frequency, body temperature) * Treatment-emergent electrocardiogram (ECG) abnormalities * Treatment-emergent laboratory abnormalities |
| Number of participants with the following clinical outcome (dead, intubated at the intensive care unit [ICU], non-intubated at the ICU, discharged from ICU to other hospital care or discharged to home). | At Days 7, 14, 21, and 30. | — |
| Change in troponin I/T and BNP/NT-proBNP | From end of PDNO infusion to Day 7. | — |
| Change in the ratio PVR/SVR | During 24 hours | Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) will be calculated from the obtained values according to the following formulas: PVR= (mean pulmonary arterial pressure \[MPAP\] - pulmonary capillary wedge pressure \[PCWP\])/cardiac output (CO) SVR= (mean arterial pressure \[MAP\] - central venous pressure \[CVP\])/CO Ratio of PVR to SVR = PVR/SVR |
| Time to obtain first negative upper respiratory tract sample in the SARS-CoV-2-rt-PCR assay | From Day 1 to Day 14 | — |
Other
| Measure | Time frame |
|---|---|
| Levels of SARS-CoV-2 virus in plasma and sputum/tracheal secretion | From Day 1 to Day 2 |
| Collection of plasma for future analysis of biomarkers such as nitrite and nitrate in plasma (µM) | From Day 1 to Day 7 |
Countries
Sweden
Outcome results
None listed